GEO DataSets

Analysis of HSCs sorted fromCrebbp+/− day 14 fetal livers. Crebbp+/− mice inevitably develop myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) within 9 to 12 months of age. Results provide insight into the molecular mechanisms underlying deregulation of HSC in MDS/MPN.

Organism:

Mus musculus

Type:

Expression profiling by array, transformed count, 2 genotype/variation sets

Platform:

GPL1261

Series:

GSE18061

8 Samples

Download data: CEL

(Submitter supplied) Myelodysplastic syndrome (MDS) is considered a disease of hematopoietic stem cell (HSC) origin. To begin to unravel the molecular mechanisms underlying the deregulation of HSCs in MDS, we performed comparative gene expression profiling on Crebbp+/- and wild type HSCs. We chose to isolate HSCs from the fetal liver (FLHSC) because at this stage there were no differences in cell number between Crebbp+/- and wild type fetal livers, suggesting no overt hematopoietic differences. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS4481

Platform:

GPL1261

8 Samples

Download data: CEL

(Submitter supplied) We found that the bone marrow microenvironment of Crebbp+/- mice was unable to properly maintain the immature stem - and progenitor pools. Instead, it stimulates myeloid differentiation that progresses into a myeloproliferative-like disease. Since CREBBP is a transcriptional co-activator, we used gene expression analysis to globally assess functional deficiencies in Crebbp+/- bone marrow stroma cells at a molecular level. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

12 Samples

Download data: CEL

(Submitter supplied) How specific genetic lesions contribute to transformation of non-malignant myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (sAML) are poorly understood. The JARID2 gene is lost by chromosomal deletions in a proportion of MPN/MDS patients who progress to sAML. In this study, genetic mouse models and patient-derived xenografts (PDX) demonstrated that Jarid2 acts as a tumor suppressor in chronic myeloid disorders. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21493

32 Samples

Download data: BW, TXT

(Submitter supplied) Increased CREB levels and upregulation of its target genes expression resulted in increased myelopoiesis and colony formation.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL, CHP

(Submitter supplied) Mutations in the RNA splicing complex member SRSF2 are found frequently in myelodysplastic syndrome and related malignancies such as chronic myelomonocytic leukemia. These mutations cluster on proline 95, with P95H the most frequent. How SRSF2P95H mutations modify hematopoiesis and promote MDS/MPN development is not clear. We have established a conditionally activatable Srsf2P95H/+ knock-in allele which, when expressed within the hematopoietic stem cell populations caused profound myeloid bias, at the expense of erythroid and lymphoid cells, and a reduced frequency and competitive repopulation of HSCs. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21273

6 Samples

Download data: GCT, ODF, XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL19057 GPL21273

14 Samples

Download data: TXT, VCF

(Submitter supplied) Mutations in the RNA splicing complex member SRSF2 are found frequently in myelodysplastic syndrome and related malignancies such as chronic myelomonocytic leukemia. These mutations cluster on proline 95, with P95H the most frequent. How SRSF2P95H mutations modify hematopoiesis and promote MDS/MPN development is not clear. We have established a conditionally activatable Srsf2P95H/+ knock-in allele which, when expressed within the hematopoietic stem cell populations caused profound myeloid bias, at the expense of erythroid and lymphoid cells, and a reduced frequency and competitive repopulation of HSCs. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

2 Samples

Download data: XLSX

(Submitter supplied) Mutations in the RNA splicing complex member SRSF2 are found frequently in myelodysplastic syndrome and related malignancies such as chronic myelomonocytic leukemia. These mutations cluster on proline 95, with P95H the most frequent. How SRSF2P95H mutations modify hematopoiesis and promote MDS/MPN development is not clear. We have established a conditionally activatable Srsf2P95H/+ knock-in allele which, when expressed within the hematopoietic stem cell populations caused profound myeloid bias, at the expense of erythroid and lymphoid cells, and a reduced frequency and competitive repopulation of HSCs. more...

Organism:

Mus musculus

Type:

Other

Platform:

GPL21273

6 Samples

Download data: TXT, VCF

(Submitter supplied) Loss of function mutations of the histone acetyltransferase CREBBP have recently been described at high frequencies across a spectrum of lymphoid malignancies. The multiple effects of this epigenetic regulator on developmental and homeostatic processes have been extensively studied, however, exactly how CREBBP functions as a tumour suppressor remains unclear. Here we use a murine model to demonstrate that loss of Crebbp in haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphoproliferative disorders (LPD). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL21103 GPL17021

30 Samples

Download data: BED, BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15401

43 Samples

Download data: CEL

(Submitter supplied) A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these “sub-haploinsufficient” cells, affecting all blood cell lineages. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15401

13 Samples

Download data: CEL

(Submitter supplied) A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these “sub-haploinsufficient” cells, affecting all blood cell lineages. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15401

30 Samples

Download data: CEL

(Submitter supplied) The presence of unspliced transcripts in hematopoietic stem cells (HSCs) and the proposed association of CREBBP with the constitutive production of unspliced RNA and with pre-mRNA processing prompted us to examine more closely an anomaly we had noted in microarray-based gene expression studies but had previously attributed to experimental noise. We noticed that more than half of the probe sets down-regulated in Crebbp+/- fetal liver HSCs (FLHSCs) relative to wild-type (WT) mapped entirely within introns, rather than detecting exonic or spliced sequences. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

31 Samples

Download data: CEL

(Submitter supplied) Fus is the gene for a member of the FET family of RNA-binding proteins often involved in chromosomal translocations to generate oncogenic fusion genes in human cancers. Fus participates in multiple cellular functions, including RNA processing and transport, transcriptional regulation, and genome integrity. We uncovered its critical role in the maintenance of hematopoietic stem cells (HSCs). Fus-/- fetal livers developed normally except for a mild reduction in numbers of colony-forming cells compared to the wild type. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

4 Samples

Download data: CEL, CHP